AI Article Synopsis
- - FBXL18 is an E3 ubiquitin ligase linked to the progression of hepatocellular carcinoma (HCC) and is found to be highly expressed in HCC tissues, correlating with poor patient survival outcomes.
- - The study revealed that FBXL18 drives HCC growth in transgenic mice by promoting the K63-linked ubiquitination of the ribosomal protein S15A (RPS15A), which stabilizes it and increases levels of the oncogenic protein SMAD3, facilitating cell proliferation.
- - Targeting the FBXL18/RPS15A/SMAD3 pathway may present a new therapeutic approach for treating HCC, as elevated FBXL18 levels were positively associated with RPS15A expression in
Article Abstract
Background: F-box and leucine-rich repeat protein 18 (FBXL18) is an E3 ubiquitin ligase that is reported to be involved in the tumorigenesis of various types of cancer. However, it remains unknown whether FBXL18 is correlated with hepatocarcinogenesis.
Methods And Results: In the current study, we found that FBXL18 was highly expressed in HCC tissues and positively associated with poor overall survival of HCC patients. FBXL18 was an independent risk factor for HCC patients. We observed that FBXL18 drove HCC in FBXL18 transgenic mice. Mechanistically, FBXL18 promoted the K63-linked ubiquitination of small-subunit ribosomal protein S15A (RPS15A) and enhanced its stability, increasing SMAD family member 3 (SMAD3) levels and translocation to the nucleus and promoting HCC cell proliferation. Moreover, the knockdown of RPS15A or SMAD3 significantly suppressed FBXL18-mediated HCC proliferation. In clinical samples, elevated FBXL18 expression was positively associated with RPS15A expression.
Conclusion: FBXL18 promotes RPS15A ubiquitination and upregulates SMAD3 expression, leading to hepatocellular carcinogenesis, and this study provides a novel therapeutic strategy for HCC treatment by targeting the FBXL18/RPS15A/SMAD3 pathway.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309527 | PMC |
| http://dx.doi.org/10.1097/HC9.0000000000000198 | DOI Listing |
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- - FBXL18 is an E3 ubiquitin ligase linked to the progression of hepatocellular carcinoma (HCC) and is found to be highly expressed in HCC tissues, correlating with poor patient survival outcomes.
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